OVERALL SUMMARY/ABSTRACT The UCLA Prostate Cancer SPORE is a multidisciplinary and translational research program focused on the development of new and innovative approaches for improving the diagnosis, prognosis, and treatment of prostate cancer patients. The program?s reach includes collaborating investigators at local institutions such as Cedars Sinai and City of Hope in order to accelerate the goal of combating prostate cancer. A particular strength of the UCLA Prostate Cancer SPORE has been its ability to leverage institutional and NCI support to attract new human capital, technology, and ideas to the field of prostate cancer. Examples of these discoveries include: (1) the development of both the androgen receptor (AR) super-antagonists enzalutamide and apalutamide, (2) the discovery of the putative human prostate cancer stem cell of origin and its association with emergence of the lethal neuroendocrine phenotype, (3) the translation of novel engineered antibodies targeting Prostate Stem Cell Antigen (PSCA) to the clinic to target, treat and image prostate (and pancreatic) cancer, (4) the elucidation of signaling cross-talk between the PTEN/PI3K, AR, and ras/MAPK pathways in castrate resistant and treatment resistant prostate cancer (CRPC), and (5) the demonstration that a low fat diet supplemented with omega-3 fatty acids has measurable effects on prostate cancer and its mechanism of action. The overall goal of this competitive renewal application is to continue to apply the diversity of talent on the UCLA campus, its sister institutions and other institutions in Southern California to the critical and evolving translational challenges in the field of prostate cancer. To achieve the long-term objectives and goals of our program, the Specific Aims of the UCLA SPORE in Prostate Cancer are: (1) to perform high-impact translational research focused on some of the major challenges in the field of prostate cancer such as cancer metastasis, castration resistance, and treatment resistance, (2) to provide organizational infrastructure and novel technologies designed specifically to support the translational research objectives of the SPORE such as administrative, fiscal, and statistical support, and (3) to develop new prostate cancer researchers and research areas to advance translational research in prostate cancer through supporting innovative research in critical areas, pilot developmental research, and career development in prostate cancer research. Through these aims, UCLA Prostate Cancer SPORE can continue to promote significant and novel discoveries with potential major impact on men with prostate cancer.